Composite polymorphisms in the ryanodine receptor 2 gene associated with arrhythmogenic right ventricular cardiomyopathy

Milting, Hendrik; Lukas, N. I.; Klauke, Bärbel; Körfer, Reiner; Perrot, Andreas; Osterziel, Karl‐Josef; Vogt, Jürgen; Peters, Stefan; Thieleczek, Rolf; Varsányi, Magdolna

doi:10.1016/j.cardiores.2006.04.004

Cited by 61 publications

(60 citation statements)

References 30 publications

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“…Here, we successfully predicted that the K897T nsSNP creates a potential phosphorylation site, which might be phosphorylated by a variety of PKs, including AGC/AKT (Table III). Also, it was proposed that a G1886S nsSNP of RYR2 (NM_001035) might generate a protein kinase C phosphorylation site (44). And our prediction result was consistent with the previous study (Table III) (44).…”

Section: Genome-wide Identification Of Potential Phossnps In Hu-supporting

confidence: 82%

“…Also, it was proposed that a G1886S nsSNP of RYR2 (NM_001035) might generate a protein kinase C phosphorylation site (44). And our prediction result was consistent with the previous study (Table III) (44). Previously, Savas and Ozcelik (16) performed a small scale analysis to identify 15 nsSNPs that might create or remove potential phosphorylation sites in 14 DNA repair-and cell cycle-related proteins.…”

Section: Genome-wide Identification Of Potential Phossnps In Hu-supporting

confidence: 80%

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PhosSNP for Systematic Analysis of Genetic Polymorphisms That Influence Protein Phosphorylation

Ren

Jiang

Gao

et al. 2010

Molecular & Cellular Proteomics

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We are entering the era of personalized genomics as breakthroughs in sequencing technology have made it possible to sequence or genotype an individual person in an efficient and accurate manner. Preliminary results from HapMap and other similar projects have revealed the existence of tremendous genetic variations among world populations and among individuals. It is important to delineate the functional implication of such variations, i.e. whether they affect the stability and biochemical properties of proteins. It is also generally believed that the genetic variation is the main cause for different susceptibility to certain diseases or different response to therapeutic treatments. Understanding genetic variation in the context of human diseases thus holds the promise for "personalized medicine." In this work, we carried out a genome-wide analysis of single nucleotide polymorphisms (SNPs) that could potentially influence protein phosphorylation characteristics in human. Here, we defined a phosphorylation-related SNP (phosSNP) as a non-synonymous SNP (nsSNP) that affects the protein phosphorylation status. Using an in-house developed kinase-specific phosphorylation site predictor (GPS 2.0), we computationally detected that ϳ70% of the reported nsSNPs are potential phosSNPs. More interestingly, ϳ74.6% of these potential phosSNPs might also induce changes in protein kinase types in adjacent phosphorylation sites rather than creating or removing phosphorylation sites directly. Taken together, we proposed that a large proportion of the nsSNPs might affect protein phosphorylation characteristics and play important roles in rewiring biological pathways. Finally, all phosSNPs were integrated into the PhosSNP 1.0 database, which was implemented in JAVA 1.5 (J2SE 5.0). The PhosSNP 1.0 database is freely available for academic researchers. Molecular & Cellular Proteomics 9:623-634, 2010.

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Section: Genome-wide Identification Of Potential Phossnps In Hu-supporting

confidence: 82%

Section: Genome-wide Identification Of Potential Phossnps In Hu-supporting

confidence: 80%

PhosSNP for Systematic Analysis of Genetic Polymorphisms That Influence Protein Phosphorylation

Ren

Jiang

Gao

et al. 2010

Molecular & Cellular Proteomics

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“…This gene is responsible for release of calcium from the sarcoplasmic reticulum by the ryanodine receptor 2 (RyR2) [Shou et al 1998]. Arrhythmogenic right ventricular cardiomyopathy (ARVC) has also been reported in people with the RyR2 gene mutation [Milting et al 2006].…”

Section: Lim Domain Binding Protein 3 (Zasp/ldp3) and Lamin A/c (Lmna)mentioning

confidence: 99%

Left ventricular noncompaction cardiomyopathy: updated review

Udeoji

Philip

Morrissey

et al. 2013

Therapeutic Advances in Cardiovascular Disease

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Abstract:The first case of noncompaction was described in 1932 after an autopsy performed on a newborn infant with aortic atresia/coronary-ventricular fistula. Isolated noncompaction cardiomyopathy was first described in 1984. A review on selected/relevant medical literature was conducted using Pubmed from 1984 to 2013 and the pathogenesis, clinical features, and management are discussed. Left ventricular noncompaction (LVNC) is a relatively rare congenital condition that results from arrest of the normal compaction process of the myocardium during fetal development. LVNC shows variability in its genetic pattern, pathophysiologic findings, and clinical presentations. The genetic heterogeneity, phenotypical overlap, and variety in clinical presentation raised the suspicion that LVNC might just be a morphological variant of other cardiomyopathies, but the American Heart Association classifies LVNC as a primary genetic cardiomyopathy. The familiar type is common and follows a X-linked, autosomal-dominant, or mitochondrial-inheritance pattern (in children). LVNC can occur in isolation or coexist with other cardiac and/or systemic anomalies. The clinical presentations are variable ranging from asymptomatic patients to patients who develop ventricular arrhythmias, thromboembolism, heart failure, and sudden cardiac death. Increased awareness over the last 25 years and improvements in technology have increased the identification of this illness and improved the clinical outcome and prognosis. LVNC is commonly diagnosed by echocardiography. Other useful diagnostic techniques for LVNC include cardiac magnetic resonance imaging, computerized tomography, and left ventriculography. Management is symptom based and patients with symptoms have a poorer prognosis. LVNC is a genetically heterogeneous disorder which can be associated with other anomalies. Making the correct diagnosis is important because of the possible associations and the need for long-term management and screening of living relatives.

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“…Single-channel recordings of CPVT-mutant RyR2 channels in planar lipid bilayers (37-39, 47, 99) revealed gain-of-function defects following PKA phosphorylation (47, 99) or caffeine stimulation (30, 40). Moreover, it has been demonstrated that CPVT-associated variants sensitize RyR2 to activation by cytosolic Ca 2+ (39, 99) and delay Ca 2+ -dependent channel inactivation (60). Alternative mechanisms for diastolic SR Ca 2+ leak through CPVT mutant RyR2 have been proposed and reviewed elsewhere (30, 37).…”

Section: The Ryanodine Receptor Macromolecular Complexmentioning

confidence: 99%

Mechanisms of Human Arrhythmia Syndromes: Abnormal Cardiac Macromolecular Interactions

Mohler

Wehrens

2007

Physiology

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Many cardiac ion channels exist within macromolecular signaling complexes, comprised of pore-forming subunits that associate with auxiliary subunits, regulatory enzymes, and targeting proteins. This complex protein assembly ensures proper modulation of channel activity and ion homeostasis. The association of genetic defects in regulatory and targeting proteins to inherited arrhythmia syndromes has led to a better understanding of the critical role these proteins play in ion channel modulation.

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Composite polymorphisms in the ryanodine receptor 2 gene associated with arrhythmogenic right ventricular cardiomyopathy

Cited by 61 publications

References 30 publications

PhosSNP for Systematic Analysis of Genetic Polymorphisms That Influence Protein Phosphorylation

PhosSNP for Systematic Analysis of Genetic Polymorphisms That Influence Protein Phosphorylation

Left ventricular noncompaction cardiomyopathy: updated review

Mechanisms of Human Arrhythmia Syndromes: Abnormal Cardiac Macromolecular Interactions

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